Keros Therapeutics has halted dosing in two arms of its Phase 2 Tropos trial evaluating cibotercept for pulmonary arterial hypertension (PAH) following the observation of pericardial effusion in some patients. The news led to a dramatic 73% drop in the company's stock price, reflecting significant investor concern about the future of the drug.
The Tropos trial is evaluating three different doses of cibotercept in PAH patients already receiving other therapies. The decision to halt dosing in the two higher-dose arms was made after reports of excess fluid buildup in the pericardial sac around the heart. According to Keros CEO Jasbir Seehra, this observation was "unanticipated" based on preclinical and healthy volunteer studies.
Impact on Cibotercept's Potential
Prior to this setback, cibotercept was viewed by some as a potential competitor to Merck's Winrevair, a drug approved for PAH that analysts project could generate $5 billion in annual sales. The hope was that cibotercept could offer improved safety and potentially superior efficacy at higher doses. However, William Blair analyst Matt Phipps suggests that regaining investor confidence in cibotercept will be difficult, even if the lower dose shows a favorable benefit/risk profile.
Trial Status and Future Plans
Keros will continue the Tropos trial with the lowest dose of cibotercept while investigating the cause of the pericardial effusion. The company aims to understand the underlying mechanism and assess the potential for the lower dose to demonstrate clinical benefit without the observed safety issues.
Broader Implications for Keros Therapeutics
While cibotercept is Keros' lead drug, the company has other assets in its pipeline. Notably, Takeda recently agreed to pay $200 million for rights to elritercept, an experimental drug for blood disorders, outside of China, Hong Kong, and Macau. This deal remains unaffected by the cibotercept setback.
